This study is an investigation into the various cellular processes involved in the healing of skeletal fractures in rats and guinea pigs. The objectives are: (1) The histochemical localization, using light and electron microscopy, of lysosomal enzymes (acid phosphatase, aryl sulfatase, inorganic trimetaphosphatase, neutral pyrophosphatase, phosphamidase and esterase) and alkaline phosphatase in all cell types participating in fracture healing. (2) An electron microscopic description of the cells found in forming callus, including periosteum and endosteum, blood vessels, and haematoma-granulation tissue. (3) The biochemical analysis of acid and alkaline phosphatase, inorganic pyrophosphatase, Beta-glucuronidase and Beta-galactosidase in healing fractures. (4) Measurement of breaking strength of healing fractures, related to age of animal, age of callus, histochemical information, and biochemical content of fracture. (5) To study the influence of factors which may increase the rate of fracture healing (zinc, PTH, and soluble collagen) or factors that have known inhibitory action on the healing process (glucagon and anticoagulants). (6) Other approaches to increasing our basic knowledge of fractures include the use of diabetic rats, a study of guinea pigs on large doses of Vitamin C, and use of diets with variations in calcium: zinc: protein ratios. The analytical techniques to be used have been developed in this laboratory specifically for the study of skeletal tissues. Histochemistry for light and electron microscopy will utilize lead-capturing and azo dye methods. Biochemical methods will utilize sensitive fluorescent measurements from methylumbelliferyl-conjugated substrates.